tbuckley/cabot-search huggingface dataset:
The effect of aroma lymphatic tressage for lower extremity edema associated with the taxane chemotherapy in patients with breast cancer: A phase 2 clinical trial.
Authors: Ju Won Kim, Yang Sun Ha, Ji Yoon Lee, Jae Hee Yang, Min Jae Lee, Eun Young Lee, Ji Young You, Seung Pil Jung, Kyong Hwa Park
Journal: Journal of Clinical Oncology (2022)

e24099 Background: Taxane-associated lower extremity edema is a distinctive adverse effect of taxane, which severely compromise patients’ quality-of-life. Aroma lymphatic tressage (ALT) has been established as a complementary technique that uses a combination of aromatherapy and hand massage to relieve distress and modulate lymphatic drainage in cancer patients. This study aimed to evaluate the symptom-relieving efficacy of a short course ALT on taxane-induced lower extremity edema. Methods: Patients treated with taxane-based chemotherapy for early or advanced stage breast cancer were screened for the study. Patients were enrolled when they presented more than CTCAE G3 of lower-extremity edema. A total of 8 sessions of ALT were applied twice a week for 4 weeks after completing taxane. The primary endpoint was to determine the leg circumference change before and after receiving ALT. Patients’ subjective degree of edema, and quality-of-life were also assessed. Results: A total of 37 patients completed all sessions of planned treatment. All of the participants were female, with the median age of 55.4-years-old. 30.8% of them were premenopausal. The median height of the patients was 157.6cm, median weight was 60.9kg, and median BMI was 1.6kg/m 2 . Most of the patients received docetaxel (87.2%). The baseline thigh, calf, and ankle circumferences were 56.5cm, 37.4cm, and 22.6cm, each. After 8 sessions of ALT, the median circumferences decreased to 54.7cm, 36.2cm, and 21.9cm. 23 (62.2%) participants experienced a 3% or more reduction in circumference change with a month of ALT. Patients’ subjective degree of edema decreased 56.9% for 4 weeks compared to baseline, while mean body weight decreased from 62.6kg to 61.2kg. All the differences before and after the ALT were statistically significant (p-value &lt; 0.0001) Most of the indicators assessing patients’ quality-of-life improved during the ALT periods, especially physical subscale (from 14.8 to 19.1, p-value &lt; 0.0001). EORTC-QLQ-C30 score also improved from 70.8 to 57.1 (p-value &lt; 0.0001). Conclusions: To our knowledge, this is the first clinical trial to evaluate clinical efficacy of ALT on taxane-associated lower extremity edema. Patients who received ALT after taxane-based chemotherapy presented significant decline of leg circumference and improvement of QoL.
Brown Adipose Tissue—A Translational Perspective
Authors: André C Carpentier, Denis P Blondin, François Haman, Denis Richard
Journal: Endocrine Reviews (2022)

Abstract Brown adipose tissue (BAT) displays the unique capacity to generate heat through uncoupled oxidative phosphorylation that makes it a very attractive therapeutic target for cardiometabolic diseases. Here, we review BAT cellular metabolism, its regulation by the central nervous and endocrine systems and circulating metabolites, the plausible roles of this tissue in human thermoregulation, energy balance, and cardiometabolic disorders, and the current knowledge on its pharmacological stimulation in humans. The current definition and measurement of BAT in human studies relies almost exclusively on BAT glucose uptake from positron emission tomography with 18F-fluorodeoxiglucose, which can be dissociated from BAT thermogenic activity, as for example in insulin-resistant states. The most important energy substrate for BAT thermogenesis is its intracellular fatty acid content mobilized from sympathetic stimulation of intracellular triglyceride lipolysis. This lipolytic BAT response is intertwined with that of white adipose (WAT) and other metabolic tissues, and cannot be independently stimulated with the drugs tested thus far. BAT is an interesting and biologically plausible target that has yet to be fully and selectively activated to increase the body’s thermogenic response and shift energy balance. The field of human BAT research is in need of methods able to directly, specifically, and reliably measure BAT thermogenic capacity while also tracking the related thermogenic responses in WAT and other tissues. Until this is achieved, uncertainty will remain about the role played by this fascinating tissue in human cardiometabolic diseases.
Development of a risk stratification model to predict oncology patient emergency room and/or hospital utilization.
Authors: Courtney C Laird, Sarah McLarty, Shirisha Reddy, Edward Thompson, Robert Cullum, William Cavers, Kayla E Friend, Kathryn D Johnson, Melissa Johlie, Christine Sawicki, Kjel Andrew Johnson
Journal: Journal of Clinical Oncology (2022)

e18664 Background: Patients diagnosed with cancer require comprehensive care management during the complex cancer care journey to improve outcomes and control healthcare costs. A care team can use risk stratification to provide patient-specific interventions to improve outcomes and reduce unplanned admissions. The purpose of this study is to evaluate specific factors that may predict a cancer patient’s likelihood of requiring unplanned emergency room (ER) visits and/or hospitalizations, which can then ultimately be used to classify patients into risk categories and match cancer patients to the appropriate level of care management. Methods: Medical claims data from oncology patients included age, gender, cancer type and co-morbidities. Stepwise multiple regression was then used to determine the correlation between predictors and patient ER and/or hospital admissions during the study period, January 1, 2021, to December 31, 2021. Akaike’s Information Criterion (AIC) was used to limit the total number of variables included in the final model to those predictive of outcomes. A logistic regression model was to determine which predictors significantly correlated with unplanned outcomes; p &lt; 0.05 was considered statistically significant. Results: 779 Medicare patients were evaluated. A total of 13 common comorbidities, patient age, gender and cancer type were explored. The final model included age, cancer type, and 6 comorbidities. Increasing age (p &lt; 0.07) and certain cancer types (cervical, pancreatic and ovarian) increased the risk of emergency room and/or hospital utilization. Metastatic cancer (p &lt; 0.007), sepsis (p &lt; 0.0003), renal failure (p &lt; 0.01), heart disease (p &lt; 0.0002), hypertension (p &lt; 0.002) and back pain (p &lt; 0.003) were also significant predictors of an ER visit and/or hospitalization. In receiver operating characteristic (ROC) analysis, our model demonstrated strong discriminative power, with an area under the ROC (AuROC) of 0.762 and p &lt; 0.05. Conclusions: This study developed and tested an algorithm to predict cancer patients for whom an ER visit and/or hospitalization outcome is more likely. The results can be used to prioritize and personalize care management resulting in improved outcomes, better allocation of care management resources, and improved overall value of care.
Immune checkpoint inhibition with PD-1 inhibitor induces cardiac dysfunction without overt myocarditis in C57BL/6J mice
Authors: T Gergely, D Kucsera, VE Toth, B Petrovich, B Agg, ZS Onodi, M Ruppert, T Radovits, B Merkely, P Ferdinandy, ZV Varga
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union’s Horizon 2020 Research and Innovation Programme under grant agreement no. 739593 “Semmelweis 250+ Kiválósági PhD Ösztöndíj” (EFOP-3.6.3-VEKOP-16-2017-00009) Gedeon Richter Talentum Foundation’s scholarship Background Immune checkpoint inhibitors have revolutionized the treatment of several form of malignancies (including metastatic melanoma) by enhancing the cytotoxic effects of T cells against cancer cells. Cancer cells evade immune surveillence by increasing the expression of T cell inhibitory molecules, also known as immune checkpoints, such as programmed cell death-1 (PD-1). Pharmacological inhibition of these molecules by immune checkpoint inhibitors (ICI) will enhance the antitumor activity of T cells. However, enhanced T cell activity may cause immune related adverse effects, including cardiotoxicity. Aims We aimed to investigate the effect of PD-1 inhibition on cardiac function and the underlying mechanisms in mice. Methods 8-10 weeks old C57BL6/J mice were treated with isotype control or anti-PD-1 antibody for 2 or 4 weeks. Cardiac function and morphology was assessed by echocardiography and histology, while the transcriptomic changes were analyzed via RNA sequencing. Nitrosative stress in the heart was assessed by immunohistochemistry and qRT-PCR. Inflammatory gene expression alterations were determined by qRT-PCR in the heart and thymus. Results Small animal echocardiography revealed cardiac dysfunction even after 2 weeks of anti-PD-1 treatment, with distinct transcriptomic changes. Nitrosative stress was found to be elevated in the myocardium due to anti-PD-1 treatment, however, histological and qRT-PCR analysis did not reveal T cell infiltration into the myocardium and only mild inflammation was seen in the heart. In contrast, inflammatory gene expression was significantly enhanced in the thymus of anti-PD-1-treated animals, where interleukin-17 showed the most prominent increase. Conclusions These findings characterize cardiac dysfunction as a form of ICI-induced cardiotoxicity, which may be mediated by increased thymic inflammatory activation and cytokine production.
CONET: copy number event tree model of evolutionary tumor history for single-cell data
Authors: Magda Markowska, Tomasz Cąkała, BłaŻej Miasojedow, Bogac Aybey, Dilafruz Juraeva, Johanna Mazur, Edith Ross, Eike Staub, Ewa Szczurek
Journal: Genome biology (2022)

Abstract Copy number alterations constitute important phenomena in tumor evolution. Whole genome single-cell sequencing gives insight into copy number profiles of individual cells, but is highly noisy. Here, we propose CONET, a probabilistic model for joint inference of the evolutionary tree on copy number events and copy number calling. CONET employs an efficient, regularized MCMC procedure to search the space of possible model structures and parameters. We introduce a range of model priors and penalties for efficient regularization. CONET reveals copy number evolution in two breast cancer samples, and outperforms other methods in tree reconstruction, breakpoint identification and copy number calling.
Seizures as treatment-emergent adverse events during glioblastoma clinical trials.
Authors: Robert O. Dillman
Journal: Journal of Clinical Oncology (2022)

e14018 Background: Seizures are not an uncommon presenting symptom of glioblastoma (GBM), and may occur following surgery for GBM. Such seizures typically can be controlled with anti-epileptics, and the risk of seizures seems to decrease after concurrent radiation therapy and temozolomide chemotherapy (RT/TMZ). However, the risk of seizures theoretically might be increased in association with a therapeutic intervention designed to enhance local inflammation at the GBM site. 33% of patients experienced one or more seizures as a treatment-emergent-adverse-event (TEAE) during a phase II clinical trial of AV-GBM-1, patient-specific dendritic cell vaccines that consist of autologous dendritic cells loaded with autologous tumor associated antigens derived from a short-term culture of self-renewing tumor cells, that were injected subcutaneously for up to six months after recovery following concurrent RT/TMZ (Bota DA et al. 2021 Society for Immunotherapy of Cancer (SITC) late-breaking abstract #952, 2021 Society of Neuro-Oncology abstract #CTIM-33). A literature search was conducted to determine reported rates of seizures as TEAE in primary GBM patients in clinical trials. Methods: Phase III trials of systemic treatment of primary GBM, and published during 2005 to 2021, were identified by searches of clinicaltrials.gov and PubMed. Published reports were reviewed for data describing the frequency of seizures reported as TEAE in text and/or summary tables. Only trials that had at least 50 patients in a standard treatment arm of surgical resection, RT/TMZ and maintenance TMZ were included. Chi square test was used to compare proportions of patients experiencing seizures in these trials. Results: Eight such randomized trials were identified. Five trials did not mention seizures as TEAE. One trial provided data only for grade 3 and 4 events: 13/229 (5.7%). The other two trials reported all seizures regardless of grade, but were limited to patient populations with O 6 -methylguanine-DNA-methyltransferase promoter methylation in one, and epidermal growth factor receptor amplification in the other. The rates of seizures in those two trials were much lower than the 19/57 (33.0%) reported with AV-GBM-1: 28/258 (10.9%, p &lt; 0.0001), and 69/372 (15.4%, p = 0.0136). Conclusions: The frequency of seizures that occur in GBM patients receiving standard RT/TMZ is not well-documented in publications of large, randomized trials. AV-GBM-1 may be associated with a higher rate of seizures because of treatment-induced inflammation at the tumor site, but a randomized trial would be needed to determine this.
Downregulation of ATP binding cassette subfamily a member 10 acts as a prognostic factor associated with immune infiltration in breast cancer.
Authors: Yen-Dun Tony Tzeng, Jim Jinn-Chyuan Sheu, Chia-Jung Li
Journal: Journal of Clinical Oncology (2022)

e13012 Background: The human ATP binding cassette (ABC) family of transporter proteins plays an important role in the maintenance of homeostasis in vivo. The aim of this study is to evaluate the potential diagnostic, prognostic, and therapeutic value of the ABCA10 gene in BRCA. Methods: In this study, a multi-step process was used to construct an immune-related genes (IRGs) based signature leveraging the expression profiles and clinical characteristics of BRCA from the Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database. An integrated immunogenomic analysis was performed to determine the association between IRGs with prognostic significance and cancer genotypes in the tumor immune microenvironment (TIME). Moreover, we performed a comprehensive in silico therapeutics screening to identify agents with subclass-specific efficacy. Results: We found that ABCA10 expression was downregulated in different subgroups of breast cancer and strongly correlated with pathological stage in BRCA patients. Low expression of ABCA10 was associated with BRCA patients showing shorter overall survival (OS). ABCA10 expression may be regulated by promoter methylation, copy number variation (CNV) and kinase, and is associated with immune infiltration. Our study also demonstrated the potential role of ABCA10 modifications in tumor microenvironment (TME) cellular infiltration. Nevertheless, the regulatory mechanism remains unknown and immunotherapy is marginal in BRCA. We demonstrate the expression of different ABCA10 modulators in breast cancer associated with genetic variants, deletions, tumor mutation burden (TMB) and TME. Mutations in ABCA10 are positively associated with different immune cells in six different immune databases. Mutations in ABCA10 and immune cell infiltration play an important role in breast cancer. Conclusions: Overall, this study provides evidence that ABCA10 could become the potential targets for precision treatment and new biomarkers in the prognosis of breast cancer.
Correction: Multicenter, single-arm, phase II trial of camrelizumab and chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma
Journal: Journal for ImmunoTherapy of Cancer (2022)

Correction: Multicenter, single-arm, phase II trial of camrelizumab and chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma
MEDB-57.<i>GNAS</i> inactivation as a driver for sonic hedgehog-activated medulloblastoma
Authors: Erin Goode, Liliana Montoya, Eric Graham, Brianna Pruniski, Curtis Simmons, Alexander Ngwube, Lindsey M Hoffman, Nishant Tiwari, Kenneth Aldape, Harper N Price, Vera Paulson, Ross Mangum
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: Sonic hedgehog (SHH)-activated medulloblastoma is one of the four consensus molecular subgroups of medulloblastoma and is typically associated with PTCH1, SUFU, and/or SMO mutations. GNAS inactivating mutations are a less commonly recognized tumorigenic driver for SHH pathway activation. CASE PRESENTATION: We report the case of an 11-month-old male who presented with a large posterior fossa mass, cerebellar tonsillar herniation, and obstructive hydrocephalus. Following a successful gross total resection, pathology was consistent with desmoplastic/nodular medulloblastoma. Tumor molecular profiling using a DNA-based, next-generation sequencing platform detected a pathogenic frameshift mutation in the GNAS gene (p.D189Mfs*14, NM_000516.4:c.565_568del) at a variant allele frequency of 81%, suggestive of biallelic GNAS inactivation. The same mutation was detected from a buccal swab sample, confirming germline GNAS inactivation. Whole genome methylation profiling was consistent with medulloblastoma subclass SHH B (infant). Concurrent with this brain tumor evaluation, a skin biopsy was performed of scattered subcutaneous, plate-like nodules distributed over the patient’s back and extremities. This revealed metaplastic-appearing cancellous bone within the dermis and subcutaneous tissue consistent with plate-like osteoma cutis. He was treated with high-dose chemotherapy followed by autologous stem cell rescue and remains disease-free 15 months from diagnosis. DISCUSSION: There have been scattered case reports describing germline loss-of-function GNAS mutations acting as tumorigenic drivers of SHH medulloblastoma. However, GNAS alterations are not covered by most standard diagnostic molecular sequencing panels for medulloblastoma. Other phenotypic manifestations of germline inactivating GNAS mutations include pseudohypoparathyroidism, pseudopseudohypoparathyroidism, progressive osseous heteroplasia, and osteoma cutis. CONCLUSION: Knowledge of the possible association between germline GNAS inactivating mutations and the development of childhood SHH-activated medulloblastoma is essential for prompt diagnosis and treatment initiation. As such, consideration should be given for inclusion of GNAS alterations in diagnostic medulloblastoma sequencing panels, especially in the setting of osteoma cutis or other endocrinopathies.
In acute stroke with a large ischemic region, endovascular therapy improved functional status at 90 d
Authors: Bruce M. Lo, Christopher R. Carpenter
Journal: Annals of Internal Medicine (2022)

ACP Journal ClubJune 2022In acute stroke with a large ischemic region, endovascular therapy improved functional status at 90 dBruce M. Lo, MD, MBA, Christopher R. Carpenter, MD, MSCBruce M. Lo, MD, MBAEastern Virginia Medical School/Sentara Norfolk General Hospital, Norfolk, Virginia, USA (B.M.L.)Search for more papers by this author, Christopher R. Carpenter, MD, MSCWashington University, School of Medicine, St. Louis, Missouri, USA (C.R.C.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/J22-0035 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationYoshimura S, Sakai N, Yamagami H, et al. Endovascular therapy for acute stroke with a large ischemic region. N Engl J Med. 2022;386:1303-13. https://pubmed.ncbi.nlm.nih.gov/35138767Clinical Impact RatingsEmergency Med: Hospitalists: Neurology: References1. Lee JS, Hwang YH, Sohn SI. Factors contributing to an efficacious endovascular treatment for acute ischemic stroke in Asian population. Neurointervention. 2021;16:91-110. [PMID: 33765729] Google Scholar2. Adusumilli G, Pederson JM, Hardy N, et al. Mechanical thrombectomy with and without intravenous tissue plasminogen activator for acute ischemic stroke: a systematic review and meta-analysis using nested knowledge. Front Neurol. 2021;12:759759. [PMID: 34975722] Google Scholar3. Rangaraju S, Haussen D, Nogueira RG, et al. Comparison of 3-month stroke disability and quality of life across modified Rankin Scale categories. Interv Neurol. 2017;6:36-41. [PMID: 28611832] Google Scholar4. Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49:e46-110. [PMID: 29367334] Google Scholar Author, Article, and Disclosure InformationAffiliations: Eastern Virginia Medical School/Sentara Norfolk General Hospital, Norfolk, Virginia, USA (B.M.L.)Washington University, School of Medicine, St. Louis, Missouri, USA (C.R.C.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=J22-0035.This article was published at Annals.org on 7 June 2022.ACP Journal Club is editorially independent from Annals of Internal Medicine. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics June 2022Volume 175, Issue 6Page: JC67KeywordsDisabilitiesDisclosureHospital medicineIschemic strokeQuality of lifeRelative riskResearch fundingSafetyStent implantationStroke ePublished: 7 June 2022 Issue Published: June 2022 Copyright & PermissionsCopyright © 2022 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Radical cystectomy video consensus: A simple and effective way to improve awareness of patients undergoing radical cystectomy
Authors: F. Esperto, F. Prata, N. Deanesi, A. Ragusa, F. Tedesco, A. Testa, A. Civitella, P. Tuzzolo, L. Romei, V.G. Crimi, L. Cacciatore, G.P. Flammia, A. Alcini, A. Salerno, S.M. Prata, R.M. Scarpa, R. Papalia
Journal: European Urology (2022)
CAIX-specific CAR-NK targeting renal cell carcinoma
Authors: J.C. Oosterwijk-Wakka, J.Y. Xu, M.C.A. De Weijert, A.N. Kenyon, P.K.J.D. De Jonge, H. Dolstra, P.F.A. Mulders, E. Oosterwijk
Journal: European Urology (2022)